Docetaxel Trihydrate

Docetaxel is a cancer (antineoplastic) medication. Docetaxel interferes with the growth of cancer cells and slows their growth and spread in the body.

Docetaxel is used in the treatment of certain forms of breast cancer, lung cancer, and prostate cancer.

Docetaxel may also be used for purposes other than those listed in this medication guide.

Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants. The chemical name for docetaxel is (2R,3S)-N-carboxy-3-phenylisoserine,N- tert -butyl ester, 13-ester with 5(beta)-20-epoxy-1,2(alpha),4,7(beta),10(beta),13(alpha)-hexahydroxytax-11-en-9-one 4-acetate 2-benzoate, trihydrate. Docetaxel has the following structural formula:

Docetaxel is a white to almost-white powder with an empirical formula of C43H53NO14กค3H2O, and a molecular weight of 861.9. It is highly lipophilic and practically insoluble in water. Docetaxel (docetaxel) Injection Concentrate is a clear yellow to brownish-yellow viscous solution. Docetaxel is sterile, non-pyrogenic, and is available in single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL) docetaxel (anhydrous). Each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80.

Docetaxel Injection Concentrate requires dilution prior to use. A sterile, non-pyrogenic, single-dose diluent is supplied for that purpose. The diluent for Docetaxel contains 13% ethanol in water for injection, and is supplied in vials.

DOSAGE AND ADMINISTRATION

Breast Cancer

In the adjuvant treatment of operable node-positive breast cancer, the recommended Docetaxel dose is 75 mg/m 2 administered 1-hour after doxorubicin 50 mg/m 2 and cyclophosphamide 500 mg/m 2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.

Non-Small Cell Lung Cancer

For treatment after failure of prior platinum-based chemotherapy, Docetaxel was evaluated as monotherapy, and the recommended dose is 75 mg/m 2 administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m 2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized, controlled trials .

For chemotherapy-naive patients, Docetaxel was evaluated in combination with cisplatin. The recommended dose of Docetaxel is 75 mg/m 2 administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m 2 over 30-60 minutes every 3 weeks.

Prostate cancer

Premedication Regimen

All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day ( e.g., 8 mg BID) for 3 days starting 1 day prior to Docetaxel administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.

For hormone-refractory metastatic prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before the Docetaxel infusion.

Dosage Adjustments During Treatment

Breast Cancer

Patients who are dosed initially at 100 mg/m 2 and who experience either febrile neutropenia, neutrophils < 500 cells/mm 3 for more than 1 week, or severe or cumulative cutaneous reactions during TAXOTERE therapy should have the dosage adjusted from 100 mg/m 2 to 75 mg/m 2 . If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m 2 to 55 mg/m 2 or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m 2 and who do not experience febrile neutropenia, neutrophils <500 cells/mm 3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during TAXOTERE therapy may tolerate higher doses. Patients who develop >/= grade 3 peripheral neuropathy should have TAXOTERE treatment discontinued entirely.

Combination Therapy with TAXOTERE in the Adjuvant Treatment of Breast Cancer

TAXOTERE in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is >/= 1,500 cells/mm 3 . Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their TAXOTERE dose reduced to 60 mg/m 2 . Patients who experience Grade 3 or 4 stomatitis should have their TAXOTERE dose decreased to 60 mg/m 2 . Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during TAXOTERE therapy should have their dosage of TAXOTERE reduced from 75 to 60 mg/m 2 . If the patient continues to experience these reactions at 60 mg/m 2 , treatment should be discontinued.

Non-Small Cell Lung Cancer

Monotherapy with TAXOTERE for NSCLC Treatment After Failure of Prior Platinum-Based Chemotherapy

Patients who are dosed initially at 75 mg/m 2 and who experience either febrile neutropenia, neutrophils <500 cells/mm 3 for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during TAXOTERE treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m 2 . Patients who develop >/= grade 3 peripheral neuropathy should have TAXOTERE treatment discontinued entirely.

Combination Therapy with TAXOTERE for Chemotherapy-Naive NSCLC

For patients who are dosed initially at TAXOTERE 75 mg/m 2 in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm 3 , in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the TAXOTERE dosage in subsequent cycles should be reduced to 65 mg/m 2 . In patients who require a further dose reduction, a dose of 50 mg/m 2 is recommended. For cisplatin dosage adjustments, see manufacturers' prescribing information.

TAXOTERE should be administered when the neutrophil count is >/= 1,500 cells/mm 3 . Patients who experience either febrile neutropenia, neutrophils < 500 cells/mm 3 for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during TAXOTERE therapy should have the dosage of TAXOTERE reduced from 75 to 60 mg/m 2 . If the patient continues to experience these reactions at 60 mg/m 2 , the treatment should be discontinued.